A method was developed to measure cerebrovascular permeability to water-soluble as well as lipid-soluble drugs. Pharmacokinetic principles for the central nervous system were established that should make it possible to calculate brain concentrations of drugs from measured plasma concentration curves and peripheral metabolic rates. Cerebrovascular integrity was not changed in rats following microwave exposure, although such exposure altered regional cerebral blood flow. Opening of the blood-brain barrier, by osmotic means or by hypertension, uncoupled cerebral blood flow from metabolism, caused brain edema, and stimulated brain glucose utilization. Osmotic opening of the blood-brain barrier was employed in rats to allow protein-bound bilirubin into the brain, as an experimental model of clinical kernicterus. It also has been used in man for allowing methotrexate into the brain, in the treatment of metastatic brain tumors.